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WO2002034264A1 - Medicaments pour traiter la sclerose laterale amyotrophique (sla) - Google Patents

Medicaments pour traiter la sclerose laterale amyotrophique (sla) Download PDF

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Publication number
WO2002034264A1
WO2002034264A1 PCT/JP2000/007994 JP0007994W WO0234264A1 WO 2002034264 A1 WO2002034264 A1 WO 2002034264A1 JP 0007994 W JP0007994 W JP 0007994W WO 0234264 A1 WO0234264 A1 WO 0234264A1
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WO
WIPO (PCT)
Prior art keywords
motor neuron
disease
lateral sclerosis
neuron disease
als
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/JP2000/007994
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English (en)
Japanese (ja)
Inventor
Ken Ikeda
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Mitsubishi Tanabe Pharma Corp
Original Assignee
Mitsubishi Pharma Corp
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Mitsubishi Pharma Corp filed Critical Mitsubishi Pharma Corp
Priority to EP00974963A priority Critical patent/EP1405637B1/fr
Priority to JP2002537315A priority patent/JP3758164B2/ja
Priority to DE60022560T priority patent/DE60022560T2/de
Priority to AT00974963T priority patent/ATE303808T1/de
Priority to US10/399,961 priority patent/US6933310B1/en
Publication of WO2002034264A1 publication Critical patent/WO2002034264A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/415—1,2-Diazoles
    • A61K31/4152—1,2-Diazoles having oxo groups directly attached to the heterocyclic ring, e.g. antipyrine, phenylbutazone, sulfinpyrazone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/06—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D231/08—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with oxygen or sulfur atoms directly attached to ring carbon atoms

Definitions

  • the present invention relates to a therapeutic agent for a motor neuron disease and a motor neuron enhancer. More specifically, the present invention relates to a remedy for exercise and exercise, which comprises 3-methyl-1-phenyl-2-pyrazolin-15-one or a physiologically acceptable salt thereof as an active ingredient. It relates to a neuron enhancer. Background art
  • Motor neuron diseases include amyotrophic lateral sclerosis (ALS), in which both primary and secondary motor neurons are impaired, and spinal muscular atrophy (SMA), in which only secondary motor neurons are impaired. Yes, other, progressive bulbar palsy, primary lateral sclerosis
  • ALS amyotrophic lateral sclerosis
  • SMA spinal muscular atrophy
  • ALS congenital polyarticular contracture
  • AMC congenital polyarticular contracture
  • ALS The main etiologies of ALS include (1) autoimmunity theory (emergence of autoantibodies to Ca channels), (2) excitatory amino acid excess and intoxication theory (increase in extracellular glutamate and glumimin). Acid transport disorders), (3) oxidative stress disorder theory (neuronal damage due to Cu / Zn superoxide dismutase (SOD) gene abnormalities and free radicals), (4) cytoskeletal disorder theory (neurofilament accumulation in motor neurons) And inclusion bodies, and (5) neurotrophic factor deficiency have been proposed as hypotheses.
  • autoimmunity theory emergence of autoantibodies to Ca channels
  • excitatory amino acid excess and intoxication theory increase in extracellular glutamate and glumimin. Acid transport disorders
  • oxidative stress disorder theory nuclear damage due to Cu / Zn superoxide dismutase (SOD) gene abnormalities and free radicals
  • SOD superoxide dismutase
  • cytoskeletal disorder theory neuroofilament
  • ALS therapeutic agent As an existing ALS therapeutic agent, there is Rilzol (Tokuhyo Hei 7-5046455) (trade name: Riltec (Rhone-Poulenc Roller)).
  • This therapeutic agent is a benzothiazole compound, which has been shown to inhibit glutamate transmission in glutamate-nergic nerves and to have a neuroprotective effect on neurodegeneration. Has been promoted and has been approved as a drug.
  • An object of the present invention is to provide a novel medicine capable of treating a motor neuron disease. More specifically, the objects of the present invention are amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA :), progressive bulbar palsy, primary lateral sclerosis (PLS), Another object of the present invention is to provide a novel drug capable of delaying the progression of a motor neuron disease such as congenital polyarticular contracture (AM C) or alleviating the symptoms thereof.
  • ALS amyotrophic lateral sclerosis
  • SMA spinal muscular atrophy
  • PLS primary lateral sclerosis
  • Another object of the present invention is to provide a novel drug capable of delaying the progression of a motor neuron disease such as congenital polyarticular contracture (AM C) or alleviating the symptoms thereof.
  • AM C congenital polyarticular contracture
  • a therapeutic agent for motor neuron disease comprising 3-methyl-1-phenyl-2-pyrazolin-5-year-old or a physiologically acceptable salt thereof as an active ingredient.
  • the therapeutic agent of the present invention comprises —Used to slow the progression of Ron's disease.
  • a motor neuron enhancer comprising, as an active ingredient, 3-methyl-1-phenyl-2-pyrazolin-15-one or a physiologically acceptable salt thereof.
  • an exercise comprising the step of administering to a patient an effective amount of 3-methyl-l-phenyl-2-birazolin-5-one or a physiologically acceptable salt thereof.
  • Methods for treating neuronal disease are provided.
  • the therapeutic method of the present invention delays the progression of a motor neuron disease.
  • an exercise comprising the step of administering to a patient an effective amount of 3-methyl-11-phenyl-2-birazolin-5-one or a physiologically acceptable salt thereof.
  • the therapeutic agent for a motor neuron disease is a therapeutic agent that slows the progression of a motor neuron disease.
  • the motoneuron disease is amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA), progressive bulbar palsy, primary lateral sclerosis (PLS), or congenital Multiple articular contracture (AMC), particularly preferably amyotrophic lateral sclerosis (ALS).
  • ALS amyotrophic lateral sclerosis
  • SMA spinal muscular atrophy
  • PLS primary lateral sclerosis
  • AMC congenital Multiple articular contracture
  • ALS amyotrophic lateral sclerosis
  • FIG. 1 shows the results of evaluating the degree of muscle contracture of the forelimbs by classifying them into four grades of 1-4.
  • the upper graph shows the results of the group administered with the medicament of the present invention, and the lower three graphs show the results of the control group.
  • FIG. 2 shows the measurement results of forelimb muscle strength.
  • FIG. 3 shows the measurement result of the weight of the right upper biceps.
  • FIG. 4 shows the measurement results of the number of spinal motoneurons.
  • the medicament of the present invention contains 3-methyl-1-phenyl-2-virazoline-5-one or a physiologically acceptable salt thereof as an active ingredient, and is used as a therapeutic agent for motor neuron disease or a motor neuron enhancer. It is characterized by being used.
  • 3-Methyl-1-phenyl-2-pyrazolin-15-one used as an active ingredient in the medicament of the present invention is a kind of free radical scavenger that suppresses lipid peroxidation.
  • 3-Methyl-1-phenyl-1-pyrazolin-15-one can be produced, for example, by the method described in the synthesis example of JP-B-5-31523, column 7.
  • the above-mentioned compounds are used as pharmaceuticals for normalizing brain function (JP-B 5-31523), inhibiting lipid peroxide production (JP-B 5-35128, compound of Example 1), anti-ulcer effect (JP-A-3-215425), blood glucose elevation inhibitory action (JP-A-3-215426), eye disease inhibitory action (JP-A-7-25765), treatment and prevention of acute renal failure (JP-A-9-1995) 52831), preservation of transplanted organs (JP-A-9-52801), prevention and treatment of skin tissue disorders (Japanese Patent Publication No. 10-279480), and prevention of necrosis of transplanted skin or transplanted tissue ( Japanese Patent Publication No. 1 79991) is known.
  • Japanese Patent Publication No. 10-279480 Japanese Patent Publication No. 10-279480
  • necrosis of transplanted skin or transplanted tissue Japanese Patent Publication No. 1 79991 is known.
  • none of these publications suggests or teaches the effects of the compounds on motor neuron
  • a physiologically acceptable salt thereof can be used in addition to the above-mentioned compound in a free form.
  • any hydrate or any solvate thereof may be used.
  • the above compounds have tautomers as shown in the chemical structural formula in the upper part of the fifth column of JP-B 5-31523, and these isomers are present in the active ingredient of the medicament of the present invention. It goes without saying that all of are included.
  • an acid addition salt or a base addition salt can be used.
  • mineral salts such as hydrochloride, sulfate, hydrobromide, or phosphate; methanesulfonate, paratoluenesulfonate, acetate, oxalate, citrate, malate, Or an organic acid salt such as a fumarate salt; a metal salt such as a sodium salt, a potassium salt, or a magnesium salt; an ammonium salt; or an organic amine salt such as ethanolamine or 2-amino-2-methyl-1-propanol.
  • the type of salt is not particularly limited as long as it is physiologically acceptable.
  • the medicament of the present invention can be administered to any animal including a human suffering from a motor neuron disease, but is preferably administered to a human.
  • the treatment of a motor neuron disease as referred to in this specification means not only a treatment for the purpose of curing the disease, but also a treatment for the purpose of delaying the progression of the disease, or the alleviation or alleviation of the symptoms of the disease. It has a broad meaning that includes all of the treatments aimed at.
  • the motor neuron disease referred to in the present invention has the broadest meaning including motor neuron disorder (motor neuropathy).
  • Motor neuron disease is a general term for a group of diseases in which the voluntary motor nervous system is selectively affected.
  • Motor neuron disease is a neurodegenerative regression disease that has a different tendency depending on the disease, but has a strong tendency to worsen.
  • Specific examples of motor neuron disease include amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA), progressive bulbar palsy, primary lateral sclerosis (PLS), or congenital Examples include, but are not limited to, multiple joint contractures (AM C).
  • Amyotrophic lateral sclerosis is an unexplained disease that begins after middle age and is characterized mainly by muscle atrophy and fasciculations.
  • Pathological findings are degeneration of the spinal anterior horn cells and medullary motor nuclei, and degeneration of the pyramidal tract.
  • Initial symptoms are mainly hand weakness, finger dysmotility, and fiber bundle spasm of the upper limb, which can be divided into upper limb type, spherical type, lower limb type, and mixed type depending on the site of onset. In both cases, the whole body muscle group is affected as the symptoms progress.
  • SMA Spinal muscular atrophy
  • cystic fibrosis is an autosomal recessive disorder after cystic fibrosis, characterized by progressive symmetric limb involvement of muscle atrophy and degeneration of the anterior horn cells of the spinal cord leading to trunk paralysis. Yes (1 in 600 newborns). SMA in children is generally divided into three clinical groups based on age of onset and clinical course.
  • Acute Werdnig-Hoffmann disease (type I) is characterized by severe generalized muscle weakness and hypotonia at birth and within the first three months of life, with two deaths from dyspnea. It usually happens within a year. The other two are intermediate (type II) and juvenile (type II, Kugelberg-Welander disorder).
  • ALS amyotrophic lateral sclerosis
  • SMA spinal muscular atrophy
  • PLS Primary lateral sclerosis
  • ALS Primary lateral sclerosis
  • PLS is a variant of ALS and is recognized as an elderly disseminated disorder.
  • Neuropathology in PLS involves cortical spinal (pyramid) degeneration, which is nearly normal at the brainstem level, but increases atrophy as they descend the spinal cord. The lower limbs are initially and most severely affected.
  • Congenital polyarticular contracture is characterized by congenital arthrodesis (1 in 3 neonates) and is a condition resulting from decreased fetal movement in the uterus.
  • AMC is caused by either oligohydramnios or a variety of disorders involving the central nervous system, skeletal muscle, or spinal cord. Since neurodegeneration and neuronal erosion occur in the anterior horn, it has been postulated that AMCs of neurogenic origin may be associated with acute spinal muscular atrophy, ie, type I SMA Weldnig-Hoffmann damage.
  • the administration route of the medicament of the present invention is not particularly limited, and the medicament can be administered orally or parenterally (for example, intravenous, intramuscular, subcutaneous or intradermal injection, or inhalation).
  • the compound or a salt thereof as an active ingredient It should preferably be administered as a preparation in the form of a pharmaceutical composition containing the active ingredient and pharmacologically and pharmaceutically acceptable additives.
  • Pharmaceutically and pharmaceutically acceptable additives include, for example, excipients, disintegrants or disintegration aids, binders, lubricants, coatings, dyes, diluents, bases, dissolution Agents, dissolution aids, tonicity agents, pH regulators, stabilizers, propellants, adhesives and the like can be used.
  • formulations suitable for oral administration include, for example, tablets, capsules, powders, fine granules, granules, solutions, and syrups.
  • formulations suitable for parenteral administration include: Examples include injections, drops, and suppositories.
  • Formulations suitable for oral administration include, as excipients, excipients such as glucose, lactose, D-mannitol, starch, or crystalline cells; carboxymethylcellulose, starch, or carboxymethylcellulose.
  • Disintegrant or disintegration aid such as calcium; binder such as hydroxypropylcellulose, hydroxypropylmethylcellulose, polyvinylpyrrolidone, or gelatin; lubricant such as magnesium stearate or talc; hydroxypropylmethylcellulose;
  • coating agents such as polyethylene glycol or titanium oxide; bases such as petrolatum, liquid paraffin, polyethylene glycol, gelatin, kaolin, glycerin, purified water, and hard fat can be used.
  • Suitable preparations for injection or infusion include solubilizing agents or solubilizing agents which can constitute aqueous or ready-to-use injections, such as distilled water for injection, physiological saline, propylene glycol, etc .; -Pharmaceutical additives such as isotonic agents such as mannitol and glycerin; pH regulators such as inorganic acids, organic acids, inorganic bases and organic bases can be used.
  • the dose of the medicament of the present invention can be appropriately selected according to various conditions such as the type of the disease to be treated, the progress of the disease or the degree of the symptoms, and the age and weight of the patient. Is preferably administered to an adult at a dose of about 0 lz gZk gl 0 mg / kg, preferably about 0.1 to 100 mg / kg, by injection or infusion per day. Examples of injections include those described in JP-A-63-132833. Is preferred.
  • the above compound which is an active ingredient of the medicament of the present invention, has high safety (LD 50 2012 mg / kg administered intraperitoneally to mice; LD 50 3,500 mg / kg administered orally to mice: Registry of Toxic Effects of Chemical Substances, 1981-1982), and has also been shown to be non-carcinogenic (National Cancer Institute Report, 89, 1978).
  • Wobbler mice exhibited shaking symptoms at the age of 3 to 4 weeks, and were diagnosed with the disease.
  • the affected mouse was treated with the drug of the present invention (3_methyl-1-phenyl-12-pyrazolin-15-one; also referred to as MC 1-186 in the figure) (1 O mg / kg) or
  • the vehicle was orally administered for 4 consecutive days by blind method.
  • the forelimb deformity of the forelimbs was 1 (limb atrophy, paw atrophy), 2 (curved digits of the toes, 3) (curved ankles, curled wrists) ⁇ and 4 (the chest of the forelimbs). It was evaluated by classifying it into four stages of flexion to the side and forelimb flexion to chest). Indicates that the symptoms worsen as you go from 1 to 4.
  • the scale of the degree of forelimb muscular contracture was analyzed by the nonparametric Wilcoxon signed-rank test. Statistical analysis of muscle strength, biceps weight, average muscle fiber diameter, and motor neuron number was performed by unpaired Student's t-test. In each test, the significance level was 5% on both sides.
  • Fig. 1 shows the results of the evaluation of the degree of muscle contracture of the forelimbs, which was classified into four levels of 1 to 4. Evaluation at baseline (3-4 weeks of age) did not differ between groups. Muscle contracture of the forelimbs progressively worsened in the mice of the control group, but administration of the medicament of the present invention slowed the progression of muscle contracture (FIG. 1).
  • Figure 2 shows the measurement results of forelimb muscle strength. Muscle strength gradually decreased in the control group, but administration of the medicament of the present invention delayed the decrease in muscle strength (FIG. 2).
  • Figure 3 shows the measurement results of the weight of the right upper biceps. Biceps weight was significantly increased by treatment with the medicament of the present invention compared to the control group (FIG. 3).
  • the mean diameter of the muscle fibers was also lower in the group treated with the medicament of the present invention (20.3 in mean soil SEM) compared to the control group (16.8 ⁇ 0.6 im in mean SEM, P ⁇ 0.01). Soil 0.8 urn P ⁇ 0.01) was significantly increased.
  • Figure 4 shows the measurement results of the number of motor neurons.
  • the number of motoneurons in the group treated with the medicament of the present invention was increased as compared to the control group (FIG. 4).
  • Wobbler mice are model animals with motor neuron disease that exhibit an autosomal recessive mode of inheritance. This animal develops with tremors in the whole body 3-4 weeks after birth. ⁇ 8 weeks Muscle weakness mainly in the forelimbs ⁇ Muscle contracture progresses rapidly. Thereafter, these neuromuscular symptoms progress slowly and have a lifespan of about 1 to 1.5 years.
  • the neuromuscular pathology of the mouse is characterized by vacuolar degeneration of motor neurons centering on the cervical spinal cord, axonal degeneration of motor nerves and neurogenic changes of skeletal muscle (H. Mitsumoto. Et al., Brain , 105 (1982) 8 ⁇ -834). Therefore, evaluating the neuroprotective effect of the therapeutic agent in the present mouse, which is 3 to 4 weeks old to 7 to 8 weeks old, is useful for evaluating the effect of the therapeutic agent on motor neuron disease.
  • the medicament containing 3-methyl-11-phenyl-12-birazolin-15-one or a physiologically acceptable salt thereof as an active ingredient according to the present invention is useful as a therapeutic drug for motor neuron disease.
  • the medicament of the present invention uses a low-molecular-weight compound as an active ingredient, it has an advantage that its transferability to the brain is relatively good.

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Abstract

L'invention concerne de nouveaux médicaments permettant de traiter la maladie du motoneurone. Ces médicaments contiennent comme principe actif de la 3-méthyl-1-phényl-2-pyrazoline-5-one ou ses sels physiologiquement acceptables.
PCT/JP2000/007994 2000-10-24 2000-11-13 Medicaments pour traiter la sclerose laterale amyotrophique (sla) Ceased WO2002034264A1 (fr)

Priority Applications (5)

Application Number Priority Date Filing Date Title
EP00974963A EP1405637B1 (fr) 2000-10-24 2000-11-13 Medicaments pour traiter la sclerose laterale amyotrophique (sla)
JP2002537315A JP3758164B2 (ja) 2000-10-24 2000-11-13 筋萎縮性側索硬化症（ａｌｓ）治療剤
DE60022560T DE60022560T2 (de) 2000-10-24 2000-11-13 Mittel zur behandlung der amyotrophischen lateralsklerose (als)
AT00974963T ATE303808T1 (de) 2000-10-24 2000-11-13 Mittel zur behandlung der amyotrophischen lateralsklerose (als)
US10/399,961 US6933310B1 (en) 2000-10-24 2000-11-13 Therapeutic agent for amyotrophic lateral sclerosis (ALS)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2000/324476 2000-10-24
JP2000324476 2000-10-24

Publications (1)

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WO2002034264A1 true WO2002034264A1 (fr) 2002-05-02

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PCT/JP2000/007994 Ceased WO2002034264A1 (fr) 2000-10-24 2000-11-13 Medicaments pour traiter la sclerose laterale amyotrophique (sla)

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US (1) US6933310B1 (fr)
EP (1) EP1405637B1 (fr)
JP (1) JP3758164B2 (fr)
AT (1) ATE303808T1 (fr)
DE (1) DE60022560T2 (fr)
ES (1) ES2248144T3 (fr)
WO (1) WO2002034264A1 (fr)

Cited By (8)

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WO2005034945A1 (fr) * 2003-10-11 2005-04-21 Thierry Schwitzguebel Utilisation de la norphenazone et de coenzyme q pour le traitement de l'arthrose, l'arthrite et l'osteo-arthrite
WO2005046680A1 (fr) * 2003-11-12 2005-05-26 Lead Chemical Co., Ltd. Agent protecteur cerebral du type administre par absorption percutanee
WO2005075434A1 (fr) * 2004-02-09 2005-08-18 Mitsubishi Pharma Corporation Nouvel agent therapeutique pour sclerose laterale amyotrophique (sla) ou maladie imputable a la sla
WO2013035712A1 (fr) 2011-09-05 2013-03-14 田辺三菱製薬株式会社 Agent médicinal pour le traitement de la sclérose latérale amyotrophique ou la prévention de l'évolution d'une phase de la sclérose latérale amyotrophique
WO2019070308A1 (fr) 2017-10-04 2019-04-11 Mitsubishi Tanabe Pharma Corporation Méthode pour traiter la sclérose latérale amyotrophique et méthode pour empêcher la progression de la sclérose latérale amyotrophique
WO2019070932A1 (fr) 2017-10-04 2019-04-11 Mitsubishi Tanabe Pharma Corporation Méthode permettant de traiter la sclérose latérale amyotrophique et méthode permettant d'empêcher la progression de la sclérose latérale amyotrophique
JPWO2019167974A1 (ja) * 2018-02-28 2021-03-18 田辺三菱製薬株式会社 ３−メチル−１−フェニル−２−ピラゾリン−５−オン原薬の分析方法、筋萎縮性側索硬化症の治療および筋萎縮性側索硬化症の進行抑制、ならびに、３−メチル−１−フェニル−２−ピラゾリン−５−オン原薬を含む薬剤の製造方法
WO2024005187A1 (fr) * 2022-07-01 2024-01-04 田辺三菱製薬株式会社 Composition et procédé d'évaluation de la réactivité de l'édaravone

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JP4302990B2 (ja) * 2001-05-11 2009-07-29 田辺三菱製薬株式会社 安定かつ高濃度であるピラゾロン誘導体を含む注射剤
US20060189566A1 (en) * 2003-02-26 2006-08-24 Miho Komatsu Muscle building agent and preventive or remedy for muscle weakening
AU2007297539A1 (en) * 2006-09-20 2008-03-27 Medivation Neurology, Inc. Methods and compositions for treating amyotrophic lateral sclerosis (ALS)
CN101524352A (zh) 2008-03-04 2009-09-09 江苏先声药物研究有限公司 一种含有3-甲基-1-苯基-2-吡唑啉-5-酮的组合物
WO2014111525A2 (fr) 2013-01-18 2014-07-24 Anaxomics Biotech, Sl Nouvelles polythérapies pour le traitement de maladies du système nerveux
IL292999A (en) 2014-11-14 2022-07-01 Voyager Therapeutics Inc Compositions and methods of treating amyotrophic lateral sclerosis (als)
CA2985219C (fr) * 2015-06-10 2020-04-28 Jiangsu Simcere Pharmaceutical Co., Ltd Utilisation d'une composition pour la fabrication d'un medicament dans le traitement de la sclerose laterale amyotrophique
PT3570819T (pt) 2017-01-17 2021-04-20 Treeway Tw001 B V Tratamento médico compreendendo a administração intestinal de edaravona
JP7107624B2 (ja) 2017-01-17 2022-07-27 ツリーウェイ ティーダブリュー００１ ビー．ブイ． エダラボンの経口又は胃内投与を含む処置
EP3618839A4 (fr) 2017-05-05 2021-06-09 Voyager Therapeutics, Inc. Compositions et méthodes de traitement de la sclérose latérale amyotrophique (sla)
WO2019008144A1 (fr) 2017-07-06 2019-01-10 Treeway Tw001 B.V. Utilisation d'édaravone dans le traitement oral de troubles neurodégénératifs induits par le stress oxydatif
TWI804518B (zh) 2017-10-16 2023-06-11 美商航海家醫療公司 肌萎縮性脊髓側索硬化症(als)之治療
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DE60022560T2 (de) 2006-06-29
US6933310B1 (en) 2005-08-23
JP3758164B2 (ja) 2006-03-22
ES2248144T3 (es) 2006-03-16
EP1405637B1 (fr) 2005-09-07
DE60022560D1 (de) 2005-10-13

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